Lipsky Benjamin A, Holroyd Kenneth J, Zasloff Michael
Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98116-1597, USA.
Clin Infect Dis. 2008 Dec 15;47(12):1537-45. doi: 10.1086/593185.
Topical antimicrobial therapy of infected diabetic foot ulcers can focus on the wound and avoid the adverse effects of systemic anti-infective agents. We compared the efficacy of outpatient treatment using an investigational topical antimicrobial peptide, pexiganan acetate cream, with the efficacy of systemic therapy using an oral fluoroquinolone antibiotic, ofloxacin, for mildly infected diabetic foot ulcers.
In 2 consecutive, double-blind, controlled trials (study 303 and study 304), we randomized diabetic patients with a mildly infected diabetic foot ulcer to receive the active topical agent or active oral antibiotic, plus a respective inactive placebo. The primary outcome of interest was clinical cure or improvement of the infection. Secondary outcomes included eradication of wound pathogens and wound healing, which was documented by a semiquantitative scoring system.
Overall, 835 patients were randomized; those in each treatment arm were similar with regard to demographic and clinical characteristics. Although study 303 failed to demonstrate equivalence, study 304 and the combined data for the 2 trials demonstrated equivalent results (within the 95% confidence interval) for topical pexiganan and oral ofloxacin in clinical improvement rates (85%-90%), overall microbiological eradication rates (42%-47%), and wound healing rates. The incidence of worsening cellulitis (2%-4%) and amputation (2%-3%) did not differ significantly between treatment arms. Bacterial resistance to ofloxacin emerged in some patients who received ofloxacin, but no significant resistance to pexiganan emerged among patients who received pexiganan.
Topical pexiganan might be an effective alternative to oral antibiotic therapy in treating diabetic patients with a mildly infected foot ulcer, and might reduce the risk of selecting antimicrobial-resistant bacteria.
感染性糖尿病足溃疡的局部抗菌治疗可针对伤口，避免全身抗感染药物的不良反应。我们比较了使用研究性局部抗菌肽醋酸派罗沙星乳膏进行门诊治疗与使用口服氟喹诺酮抗生素氧氟沙星进行全身治疗对轻度感染性糖尿病足溃疡的疗效。
在两项连续的双盲对照试验（研究303和研究304）中，我们将患有轻度感染性糖尿病足溃疡的糖尿病患者随机分组，分别接受活性局部用药或活性口服抗生素，外加各自的非活性安慰剂。主要关注的结局是感染的临床治愈或改善。次要结局包括伤口病原体的清除和伤口愈合，通过半定量评分系统记录。
总体而言，835例患者被随机分组；各治疗组患者在人口统计学和临床特征方面相似。尽管研究303未能证明等效性，但研究304以及两项试验的合并数据显示，局部用醋酸派罗沙星和口服氧氟沙星在临床改善率（85%-90%）、总体微生物清除率（42%-47%）和伤口愈合率方面的结果相当（在95%置信区间内）。治疗组之间蜂窝织炎恶化（2%-4%）和截肢（2%-3%）的发生率无显著差异。接受氧氟沙星治疗的部分患者出现了对氧氟沙星的细菌耐药性，但接受醋酸派罗沙星治疗的患者中未出现对醋酸派罗沙星的显著耐药性。
局部用醋酸派罗沙星可能是治疗轻度感染性足溃疡糖尿病患者口服抗生素治疗的有效替代方法，并可能降低选择抗菌耐药菌的风险。
